Abstract
Chemotherapy-induced pain is a dose-limiting condition that affects 30% of patients undergoing chemotherapy. We found that gut microbiota promotes the development of chemotherapy-induced mechanical hyperalgesia. Oxaliplatin-induced mechanical hyperalgesia was reduced in germ-free mice and in mice pretreated with antibiotics. Restoring the microbiota of germ-free mice abrogated this protection. These effects appear to be mediated, in part, by TLR4 expressed on hematopoietic cells, including macrophages.
MeSH terms
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Animals
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Antineoplastic Agents / toxicity*
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Cells, Cultured
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Female
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Gastrointestinal Microbiome / drug effects
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Gastrointestinal Microbiome / physiology*
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Hyperalgesia / chemically induced*
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Hyperalgesia / metabolism*
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Hyperalgesia / microbiology
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Inflammation Mediators / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Organoplatinum Compounds / toxicity
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Oxaliplatin
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Pain / chemically induced*
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Pain / metabolism*
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Pain / microbiology
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Pain Measurement / methods
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Random Allocation
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Rats
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Rats, Sprague-Dawley
Substances
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Antineoplastic Agents
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Inflammation Mediators
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Organoplatinum Compounds
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Oxaliplatin